DESCRIPTION: Sickle cell anemia is one of the most common and devastating hereditary disorders with significant morbidity and mortality affecting individuals of African American heritage. No safe, effective therapy is yet available. Within the last few years, hydroxyurea has been used in an increasing number of sickle cell anemia patients. However, hydroxyurea is a chemotherapeutic agent with myelosuppressive effects and its long term safety is still unknown. An ideal agent would be one that is readily available, effective and safe even with chronic use. Based on previous data from this laboratory on sickle red blood cell metabolism, we have conducted a pilot study recently using L-glutamine as an oral agent. The four week open label study involving seven homozygous hemoglobin S patients showed promising results by demonstrating improvement in redox potential and decrease in chronic pain in all patients. In addition a subsequent 12 week study involving 4 patients showed significant decrease in the frequency of painful sickle crises. On the basis of these data we propose to expand the study of L-glutamine therapy for sickle cell anemia to a double blind study to observe objectively the effect of the amino acid in sickle cell anemia patients in terms of their clinical status and hematological parameters. Our long term goal is to establish the usefulness and safety of L-glutamine in therapy of sickle cell anemia. Our specific aims in this project are to determine the effect of oral L-glutamine on 1) sickle red blood cells at cellular and biochemical level, 2) clinical status of the sickle cell anemia patients including the incidence of painful crisis, narcotic requirement for acute or chronic pain, 3) sickle cell anemia patients' hematological parameters including hemoglobin, hematocrit, reticulocyte count,and hexokinase level, and 4) adverse effects attributable to L-glutamine. L-glutamine is an amino acid that has been used widely for other purposes and shown to be safe by others. It is also inexpensive and readily available. The pilot data are promising. This project will provide the pathophysiologic basis for the use of L-glutamine and will evaluate the efficacy of L-glutamine in the therapy of sickle cell anemia.